[en] The stress response (SR) can block inflammatory gene expression by preventing activation of transcription factor nuclear factor-kappa B (NF-kappaB). As inflammatory gene expression contributes to the pathogenesis of demyelinating diseases, we tested the effects of the SR on the progression of the demyelinating disease experimental autoimmune encephalomyelitis (EAE). EAE was actively induced in C57BL/6 mice using an encephalitogenic myelin oligodendrocyte glycoprotein (MOG(35-55)) peptide. Whole body hyperthermia was used to induce a heat shock response (HSR) in immunized mice 2 days after the booster MOG(35-55) peptide injection. The HSR reduced the incidence of EAE by 70%, delayed disease onset by 6 days, and attenuated disease severity. The HSR attenuated leukocyte infiltration into CNS assessed by quantitation of perivascular infiltrates, and by reduced staining for CD4 and CD25 immunopositive T-cells. T-cell activation, assessed by the production of interferon gamma (IFNgamma) in response to MOG(35-55), was also decreased by the HSR. The HSR reduced inflammatory gene expression in the brain that normally occurs during EAE, including the early increase in RANTES (regulated on activation of normal T-cell expressed and secreted) expression, and the later expression of the inducible form of nitric oxide synthase. The early activation of transcription factor NF-kappaB was also blocked by the HSR. The finding that the SR reduces inflammation in the brain and the clinical severity of EAE opens a novel therapeutic approach for prevention of autoimmune diseases.
Disciplines :
Neurology
Author, co-author :
HENEKA, Michael ; Department of Neurology, University of Bonn, Bonn, Germany Department of Anesthesiology, University of Illinois, Chicago, Illinois, USA
Sharp, Anthony; Department of Anesthesiology, University of Illinois, Chicago, IL, United States
Murphy, Patricia; Department of Anesthesiology, University of Illinois, Chicago, IL, United States
Lyons, Jeri-Anne; Department of Neurology, Washington University, School of Medicine, St. Louis, MO, United States
Dumitrescu, Lucia; Department of Neurology, University of Bonn, Bonn, Germany
Feinstein, Douglas L.; Department of Anesthesiology, University of Illinois, Chicago, IL, United States ; MC 519, Chicago, IL 60612, United States
External co-authors :
yes
Language :
English
Title :
The heat shock response reduces myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis in mice.
Ali A., Bharadwaj S., O'Carroll R., Ovsenek N. (1998) HSP90 interacts with and regulates the activity of heat shock factor 1 in Xenopus oocytes. Mol. Cell Biol. 18:4949-4960.
Ayad O., Stark J.M., Fiedler M.M., Menendez I.Y., Ryan M.A., Wong H.R. (1998) The heat shock response inhibits RANTES gene expression in cultured human lung epithelium. J. Immunol. 161:2594-2599.
Bagatell R., Paine-Murrieta G.D., Taylor C.W., Pulcini E.J., Akinaga S., Benjamin I.J., Whitesell L. (2000) Induction of a heat shock factor 1-dependent stress response alters the cytotoxic activity of hsp90-binding agents. Clin. Cancer Res. 6:3312-3318.
Breithaupt T.B., Vazquez A., Baez I., Eylar E.H. (1996) The suppression of T cell function and NF (kappa) B expression by serine protease inhibitors is blocked by N-acetylcysteine. Cell Immunol. 173:124-130.
Cobb R.R., Felts K.A., Parry G.C., Mackman N. (1996) Proteasome inhibitors block VCAM-1 and ICAM-1 gene expression in endothelial cells without affecting nuclear translocation of nuclear factor-kappa B. Eur. J. Immunol. 26:839-845.
Colville-Nash P.R., Qureshi S.S., Willis D., Willoughby D.A. (1998) Inhibition of inducible nitric oxide synthase by peroxisome proliferator-activated receptor agonists: Correlation with induction of heme oxygenase 1. J. Immunol. 161:978-984.
DeMeester S.L., Buchman T.G., Qiu Y., Jacob A.K., Dunnigan K., Hotchkiss R.S., Karl I., Cobb J.P. (1997) Heat shock induces IkappaB-alpha and prevents stress-induced endothelial cell apoptosis. Arch. Surg. 132:1283-1287.
Fawcett T.W., Xu Q., Holbrook N.J. (1997) Potentiation of heat stress-induced hsp70 expression in vivo by aspirin. Cell Stress Chaperones 2:104-109.
Feinstein D.L., Galea E., Aquino D.A., Li G.C., Xu H., Reis D.J. (1996) Heat shock protein 70 suppresses astroglial-inducible nitric-oxide synthase expression by decreasing NFkappaB activation. J. Biol. Chem. 271:17724-17732.
Feinstein D.L., Galea E., Reis D.J. (1997) Suppression of glial nitric oxide synthase induction by heat shock: Effects on proteolytic degradation of I kappa B-alpha. Nitric Oxide Biol. Chem. 1:167-176.
Galea E., Reis D.J., Feinstein D.L. (1994) Cloning and expression of inducible nitric oxide synthase from rat astrocytes. J. Neurosci. Res. 37:406-414.
Galea E., Bhat N.R., Feinstein D.L. (2000) Transcriptional regulation of the inflammatory nitric oxide synthase gene: Convergence of cytosolic and nuclear signals. Elect. J. Pathol. Histol. 5:5.
Gveric D., Kaltschmidt C., Cuzner M.L., Newcombe J. (1998) Transcription factor NF-kappaB and inhibitor I kappaBalpha are localized in macrophages in active multiple sclerosis lesions. J. Neuropathol. Exp. Neurol. 57:168-178.
Hauser G.J., Dayao E.K., Wasserloos K., Pitt B.R., Wong H.R. (1996) HSP induction inhibits iNOS mRNA expression and attenuates hypotension in endotoxin-challenged rats. Am. J. Physiol. 271.
Heneka M.T., Sharp A., Klockgether T., Gavrilyuk V., Feinstein D.L. (2000) The heat shock response inhibits NF-kB activation, nitric oxide synthase type 2 expression, and macrophage/microglial activation in brain. J. Cereb. Blood Flow Metab. 20:800-811.
Hotchkiss R., Nunnally I., Lindquist S., Taulien J., Perdrizet G., Karl I. (1993) Hyperthermia protects mice against the lethal effects of endotoxin. Am. J. Physiol. 265.
Housby J.N., Cahill C.M., Chu B., Prevelige R., Bickford K., Stevenson M.A., Calderwood S.K. (1999) Non-steroidal antiinflammatory drugs inhibit the expression of cytokines and induce HSP70 in human monocytes. Cytokine 11:347-358.
Hvas J., McLean C., Justesen J., Kannourakis G., Steinman L., Oksenberg J.R., Bernard C.C. (1997) Perivascular T cells express the pro-inflammatory chemokine RANTES mRNA in multiple sclerosis lesions. Scand. J. Immunol. 46:195-203.
Johns T.G., Kerlero D.R., Menon K.K., Abo S., Gonzales M.F., Bernard C.C. (1995) Myelin oligodendrocyte glycoprotein induces a demyelinating encephalomyelitis resembling multiple sclerosis. J. Immunol. 154:5536-5541.
Juedes A.E., Hjelmstrom P., Bergman C.M., Neild A.L., Ruddle N.H. (2000) Kinetics and cellular origin of cytokines in the central nervous system: Insight into mechanisms of myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis. J. Immunol. 164:419-426.
Kaltschmidt C., Kaltschmidt B., Lannes-Vieira J., Kreutzberg G.W., Wekerle H., Baeuerle P.A., Gehrmann J. (1994) Transcription factor NF-kappa B is activated in microglia during experimental autoimmune encephalomyelitis. J. Neuroimmunol. 55:99-106.
Lee B.S., Chen J., Angelidis C., Jurivich D.A., Morimoto R.I. (1995) Pharmacological modulation of heat shock factor 1 by antiinflammatory drugs results in protection against stress-induced cellular damage. Proc. Natl. Acad. Sci. USA 92:7207-7211.
Lee J.I., Burckart G.J. (1998) Nuclear factor kappa B: Important transcription factor and therapeutic target. J. Clin. Pharmacol. 38:981-993.
Linington C., Lassmann H. (1987) Antibody responses in chronic relapsing experimental allergic encephalomyelitis: Correlation of serum demyelinating activity with antibody titre to the myelin/oligodendrocyte glycoprotein (MOG). J. Neuroimmunol. 17:61-69.
Meng X., Shames B.D., Ao L., Meldrum D.R., Chan D., Banerjee A., Harken A.H. (1999) Heat shock protein 72 suppresses macrophage TNF-alpha production by inhibition of NF kappa B intranuclear translocation. Shock 11:138.
Morimoto R.I., Santoro M.G. (1998) Stress-inducible responses and heat shock proteins: New pharmacologic targets for cytoprotection. Nat. Biotechnol. 16:833-838.
Moriuchi H., Moriuchi M., Fauci A.S. (1997) Nuclear factor-kappa B potently up-regulates the promoter activity of RANTES, a chemokine that blocks HIV infection. J. Immunol. 158:3483-3491.
Moseley P.L. (1998) Heat shock proteins and the inflammatory response. Ann. N. Y. Acad. Sci. 856:206-213.
Otremski I., Erling G., Cohen Z., Newman R.J. (1994) The effect of hyperthermia (42.5 degrees c) on zymosan-induced synovitis of the knee. Br. J. Rheumatol. 33:721-723.
Ribeiro S.P., Villar J., Downey G.P., Edelson J.D., Slutsky A.S. (1994) Sodium arsenite induces heat shock protein-72 kilodalton expression in the lungs and protects rats against sepsis. Crit. Care Med. 22:922-929.
Rossi A., Elia G., Santoro M.G. (1997) Inhibition of nuclear factor kappa B by prostaglandin A1: An effect associated with heat shock transcription factor activation. Proc. Natl. Acad. Sci. USA 94:746-750.
Santoro M.G. (2000) Heat shock factors and the control of the stress response. Biochem. Pharmacol. 59:55-63.
Scarim A.L., Heitmeier M.R., Corbett J.A. (1998) Heat shock inhibits cytokine-induced nitric oxide synthase expression by rat and human islets. Endocrinology 139:5050-5057.
Simon M.M., Reikerstorfer A., Schwarz A., Krone C., Luger T.A., Jaattela M., Schwarz T. (1995) Heat shock protein 70 overexpression affects the response to ultraviolet light in murine fibroblasts evidence for increased cell viability and suppression of cytokine release. J. Clin. Invest. 95:926-933.
Snyder Y.M., Guthrie L., Evans G.F., Zuckerman S.H. (1992) Transcriptional inhibition of endotoxin induced monokine synthesis following heat shock in murine peritoneal macrophages. J. Leukocyte Biol. 51:181-187.
Sorensen T.L., Tani M., Jensen J., Pierce V., Lucchinetti C., Folcik V.A., Qin S., Rottman J., Sellebjerg F., Strieter R.M., Frederiksen J.L., Ransohoff R.M. (1999) Expression of specific chemokines and chemokine receptors in the central nervous system of multiple sclerosis patients. J. Clin. Invest. 103:807-815.
Spiecker M., Peng H.B., Liao J.K. (1997) Inhibition of endothelial vascular cell adhesion molecule-I expression by nitric oxide involves the induction and nuclear translocation of IkappaBalpha. J. Biol. Chem. 272:30969-30974.
Steffen B.J., Butcher E.C., Engelhardt B. (1994) Evidence for involvement of ICAM-1 and VCAM-1 in lymphocyte interaction with endothelium in experimental autoimmune encephalomyelitis in the central nervous system in the SJL/J mouse. Am. J. Pathol. 145:189-201.
Storch M.K., Stefferl A., Brehm U., Weissert R., Wallstrom E., Kerschensteiner M., Olsson T., Linington C., Lassmann H. (1998) Autoimmunity to myelin oligodendrocyte glycoprotein in rats mimics the spectrum of multiple sclerosis pathology. Brain Pathol. 8:681-694.
Vanderlugt C.L., Rahbe S.M., Elliott P.J., Dal Canto M.C., Miller S.D. (2000) Treatment of established relapsing experimental autoimmune encephalomyelitis with the proteasome inhibitor PS-519. J. Autoimmun. 14:205-211.
De Vera M.E., Wong J.M., Zhou J.Y., Tzeng E., Wong H.R., Billiar T.R., Geller D.A. (1996) Cytokine-induced nitric oxide synthase gene transcription is blocked by the heat shock response in human liver cells. Surgery 120:144-149.
Villar J., Ribeiro S.P., Mullen J.B., Kuliszewski M., Post M., Slutsky A.S. (1994) Induction of the heat shock response reduces mortality rate and organ damage in a sepsis-induced acute lung injury model. Crit. Care Med. 22:914-921.
Welch W.J. (1992) Mammalian stress response: Cell physiology, structure/function of stress proteins, and implications for medicine and disease. Physiol. Rev. 72:1063-1081.
Willenborg D.O., Staykova M.A., Cowden W.B. (1999) Our shifting understanding of the role of nitric oxide in autoimmune encephalomyelitis: A review. J. Neuroimmunol. 100:21-35.
Wong H.R., Finder J.D., Wasserloos K., Pitt B.R. (1995) Expression of iNOS in cultured rat pulmonary artery smooth muscle cells is inhibited by the beat shock response. Am. J. Physiol. 269.
Wong H.R., Ryan M., Wispe J.R. (1997) The heat shock response inhibits inducible nitric oxide synthase gene expression by blocking I kappa-B degradation and NF-kappa B nuclear translocation. Biochem. Biophys. Res. Commun. 231:257-263.
Wong H.R., Ryan M.A., Menendez I.Y., Wispe J.R. (1999) Heat shock activates the I-kappaBalpha promoter and increases I-kappaBalpha mRNA expression. Cell Stress Chaperones 4:1-7.
